Introduction
Methods
Study population
Acquisition of Cardiovascular magnetic resonance images
Cardiovascular magnetic resonance image analysis
Cine image analysis
4D flow analysis
Cardiopulmonary exercise test
Reproducibility
Statistical analysis
Results
Subject characteristics and ventricular function
Healthy control (n = 51) | PAH (n = 45) |
P
| |
---|---|---|---|
Demographics and clinical parameters
| |||
Age, years | 46 ± 14 | 46 ± 11 | 0.828 |
Sex, M/F | 17/34 | 7/38 | 0.059 |
Height, cm | 163 ± 8 | 159 ± 8 |
0.017
|
Weight, kg | 60 ± 11 | 61 ± 13 | 0.515 |
Body surface area, m2 | 1.64 ± 0.17 | 1.64 ± 0.19 | 0.935 |
Body mass index, kg/m2 | 22.4 ± 3.1 | 24.1 ± 4.6 |
0.032
|
Systolic blood pressure, mmHg | 126 ± 19 | 119 ± 20 | 0.074 |
Diastolic blood pressure, mmHg | 75 ± 13 | 71 ± 14 | 0.087 |
Heart rate, bpm | 71 ± 14 | 82 ± 16 |
0.001
|
NT–proBNP, pg/mL* |
–
| 207 (337) |
–
|
Functional class > WHO I, n (%) |
–
| 18 (40%) |
–
|
Types of PAH | |||
Idiopathic PAH, n (%) |
–
| 23 (51%) |
–
|
Heritable PAH, n (%) |
–
| 4 (9%) |
–
|
PAH associated with connective tissue disease, n (%) |
–
| 13 (29%) |
–
|
Systemic sclerosis, n (%) |
–
| 4 (31%) |
–
|
Mixed connective tissue disease, n (%) |
–
| 3 (23%) |
–
|
Systemic lupus erythematosus, n (%) |
–
| 3 (23%) |
–
|
Sjogren syndrome, n (%) |
–
| 2 (15%) |
–
|
Anti–synthetase syndrome, n (%) |
–
| 1 (8%) |
–
|
PAH associated with congenital heart disease, n (%) |
–
| 5 (11%) |
–
|
Atrial septal defect repaired, n (%) |
–
| 3 (60%) |
–
|
Atrial septal defect unrepaired, n (%) |
–
| 1 (20%) |
–
|
Pulmonary atresia with ventricular septal defect, n (%) |
–
| 1 (20%) |
–
|
Medical history
| |||
Diabetes mellitus, n (%) | – | 5 (11.1%) | – |
Hypertension, n (%) | – | 7 (15.6%) | – |
Hyperlipidemia, n (%) | – | 3 (6.7%) | – |
Medication
| |||
β–Blocker, n (%) | – | 3 (6.7%) | – |
Calcium channel blockers, n (%) | – | 0 (0%) | – |
Diuretics, n (%) | – | 6 (13.3%) | – |
Anticoagulants, n (%) | – | 10 (22.2%) | – |
ERAs, n (%) | – | 24 (53.3%) | – |
Prostanoids, n (%) | – | 0 (0%) | – |
Digoxin, n (%) | – | 12 (26.7%) | – |
Corticosteroids, n (%) | – | 4 (8.9%) | – |
PDIs, n (%) | – | 26 (57.8%) | – |
Right heart catheterization
| |||
RAP, mm Hg |
–
| 9 ± 6 | – |
mPAP, mm Hg |
–
| 48 ± 14 | – |
PCWP, mm Hg |
–
| 12 ± 5 | – |
PVR, Wood units |
–
| 11.1 ± 7.0 | – |
RV systolic pressure, mmHg |
–
| 75 ± 25 | – |
LV function
| |||
LV mass index, g/m2 | 39 ± 8 | 37 ± 15 | 0.383 |
LVEDV index, ml/m2 | 76 ± 11 | 76 ± 34 | 0.993 |
LVESV index, ml/m2 | 32 ± 6 | 30 ± 21 | 0.516 |
LV stroke volume index, ml/m2 | 44 ± 7 | 47 ± 15 | 0.399 |
LVEF, % | 59 ± 5 | 62 ± 9 |
0.011
|
RV function
| |||
RVEDV index, ml/m2 | 74 ± 13 | 102 ± 41 |
< 0.001
|
RVESV index, ml/m2 | 35 ± 8 | 61 ± 31 |
< 0.001
|
RV stroke volume index, ml/m2 | 40 ± 6 | 41 ± 20 | 0.728 |
RVEF, % | 54 ± 6 | 42 ± 12 |
< 0.001
|
RVEDV/LVEDV | 0.97 ± 0.10 | 1.43 ± 0.64 |
< 0.001
|
RV mass, g | 25.6 ± 5.3 | 39.2 ± 12.4 |
< 0.001
|
RV/LV mass | 0.39 ± 0.06 | 0.58 ± 0.19 |
< 0.001
|
TAPSE, mm | 19.8 ± 2.8 | 15.0 ± 3.9 |
< 0.001
|
RV GLS, % | 24.3 ± 3.9 | 17.9 ± 4.7 |
< 0.001
|
Right atrial area (end–systole), cm2 | 19.3 ± 4.0 | 25.3 ± 11.2 |
0.001
|
PA RAC, % | 56 ± 20 | 25 ± 13 |
< 0.001
|
Cardiopulmonary exercise test
Healthy control (n = 51) | PAH (n = 45) |
P
1,2
| |
---|---|---|---|
LV 4D flow | |||
Direct flow, % | 34 (10) | 31 (12) | 0.474 |
Retained inflow, % | 17 (5) | 17 (8) | 0.607 |
Delayed ejection flow, % | 17 (5) | 16 (7) | 0.020 |
Residual volume, % | 33 (6) | 36 (10) | 0.042 |
Peak systolic KEIEDV, µJ/ml | 16.1 (5.1) | 19.3 (15.0) | 0.012 |
Average systolic KEIEDV, µJ/ml | 8.9 (3.1) | 11.5 (8.0) | 0.025 |
Peak E–wave KEIEDV, µJ/ml | 27.0 (12.0) | 19.0 (17.4) |
0.002
|
RV 4D flow
| |||
Direct flow, % | 37 (7) | 24 (16) |
< 0.001
|
Retained inflow, % | 16 (6) | 16 (5) | 0.956 |
Delayed ejection flow, % | 17 (5) | 14 (6) | 0.017 |
Residual volume, % | 29 (10) | 44 (16) |
< 0.001
|
Peak systolic KEIEDV, µJ/ml | 21.2 (8.5) | 19.4 (18.3) | 0.521 |
Average systolic KEIEDV, µJ/ml | 12.2 (4.5) | 10.4 (6.9) | 0.070 |
Peak E–wave KEIEDV, µJ/ml | 13.9 (7.6) | 8.4 (6.3) |
< 0.001
|
KE discordance | 1.30 (0.53) | 0.94 (0.66) |
< 0.001
|
Fractional flow ratio | 1.24 (0.60) | 0.51 (0.40) |
< 0.001
|
CPET
| |||
Peak VO2, ml/kg/min | 22.6 (10.5) | 13.2 (4.4) |
< 0.001
|
% predicted peak VO2, % | 87 (33) | 48 (23) |
< 0.001
|
VE/VCO2 slope | 27 (4) | 41 (10) |
< 0.001
|
Flow components and kinetic energy
Association of 4D flow CMR parameters with remodelling index, RV function and CPET outcomes
Univariate analysis | Stepwise multivariable analysis | |||
---|---|---|---|---|
Coefficient (95% CI)
|
P
value
|
Coefficient (95% CI)
|
P
value
| |
Determinants of RV function (RVEF)
| ||||
RA area, cm2 | − 0.619 (− 0.839, − 0.398) | < 0.001 | – | 0.348 |
TAPSE, mm | 1.362 (0.900, 1.823) | < 0.001 |
–
| 0.514 |
RV GLS, %
| 1.430 (1.136, 1.723) | < 0.001 |
0.596 (0.281, 0.911)
|
< 0.001
|
RV direct flow, %
| 0.820 (0.686, 0.954) | < 0.001 |
0.587 (0.426, 0.748)
|
< 0.001
|
RV retained inflow, % | 0.076 (− 0.404, 0.556) | 0.754 | Excluded | |
RV delayed ejection flow, % | 0.208 (− 0.310, 0.726) | 0.428 | Excluded | |
RV residual volume, % | − 0.649 (− 0.779, − 0.519) | < 0.001 | – | 0.378 |
RV peak systolic KEiEDV, µJ/ml | 0.370 (0.141, 0.600) | 0.002 |
0.198 (0.061, 0.336)
|
0.005
|
RV average systolic KEiEDV, µJ/ml | 0.747 (0.278, 1.216) | 0.002 | – | 0.802 |
RV peak E–wave KEiEDV, µJ/ml | 0.048 (− 0.207, 0.303) | 0.710 | Excluded | |
KE discordance | 9.393 (5.136, 13.65) | < 0.001 | – | 0.846 |
Fractional flow ratio | 11.964 (9.129, 14.80) | < 0.001 | – | 0.118 |
R–squared, multivariable | 0.698 | |||
Determinants of adverse RV remodelling (Ln(RVEDV/LVEDV))*
| ||||
RVEF, % | − 0.025 (− 0.033, − 0.017) | < 0.001 | – | 0.997 |
RA area, cm2
| 0.042 (0.034, 0.050) | < 0.001 |
0.017 (0.011, 0.023)
|
< 0.001
|
TAPSE, mm
| − 0.051 (− 0.073, − 0.028) | < 0.001 |
− 0.019 (− 0.031, − 0.007)
|
0.002
|
RV GLS, % | − 0.049 (− 0.065, − 0.033) | < 0.001 | – | 0.520 |
RV direct flow, %
| − 0.030 (− 0.038, − 0.022) | < 0.001 |
− 0.008 (− 0.013, − 0.002)
|
0.007
|
RV retained inflow, % | 0.006 (− 0.016, 0.028) | 0.589 | Excluded | |
RV delayed ejection flow, % | 0.005 (− 0.019, 0.028) | 0.703 | Excluded | |
RV residual volume, % | 0.021 (0.014, 0.028) | < 0.001 | – | 0.385 |
RV peak systolic KEiEDV, µJ/ml | 0.003 (− 0.008, 0.014) | 0.628 | Excluded | |
RV average systolic KEiEDV, µJ/ml | 0.015 (–0.008, 0.037) | 0.196 | Excluded | |
RV peak E–wave KEiEDV, µJ/ml | 0.008 (− 0.004, 0.019) | 0.201 | Excluded | |
KE discordance | − 0.129 (− 0.342, 0.083) | 0.231 | Excluded | |
Fractional flow ratio | − 0.393 (− 0.544, − 0.241) | < 0.001 |
–
| 0.096 |
R–squared, multivariable | 0.588 | |||
Determinants of exercise capacity (Ln(% predicted peak VO2))* | ||||
RVEF, % | 0.021 (0.014, 0.028) | < 0.001 | – | 0.228 |
RA area, cm2 | − 0.018 (− 0.028, − 0.008) | 0.001 | – | 0.418 |
TAPSE, mm
| 0.055 (0.036, 0.074) | < 0.001 |
0.035 (0.014, 0.055)
|
0.001
|
RV GLS, % | 0.036 (0.021, 0.051) | < 0.001 | – | 0.096 |
RV direct flow, %
| 0.023 (0.015, 0.030) | < 0.001 |
0.016 (0.008, 0.024)
|
< 0.001
|
RV retained inflow, % | − 0.006 (− 0.025, 0.014) | 0.578 | Excluded | |
RV delayed ejection flow, % | 0.019 (− 0.002, 0.040) | 0.073 | Excluded | |
RV residual volume, % | − 0.019 (− 0.025, − 0.012) | < 0.001 |
–
| 0.209 |
RV peak systolic KEiEDV, µJ/ml | − 0.003 (− 0.013, 0.007) | 0.553 | Excluded | |
RV average systolic KEiEDV, µJ/ml | − 0.002 (− 0.023, 0.018) | 0.823 | Excluded | |
RV peak E–wave KEiEDV, µJ/ml | − 0.007 (− 0.018, 0.003) | 0.164 | Excluded | |
KE discordance | 0.245 (0.060, 0.430) | 0.010 | – | 0.753 |
Fractional flow ratio | 0.331 (0.193, 0.470) | < 0.001 | – | 0.641 |
R–squared, multivariable | 0.361 |
\({\chi }^{2}\)for RVEF | Total\({\chi }^{2}\)for whole model (RVEF + RV direct flow) |
P
| |
---|---|---|---|
Discriminating adverse RV remodelling | 41.36 | 54.74 |
0.001
|
Discriminating impaired exercise capacity (% predicted peak VO2 ≤ 65%) | 40.91 | 49.15 |
0.004
|
Discriminating impaired exercise capacity (VE/VCO2 slope ≥ 36) | 34.85 | 46.45 |
0.001
|
Discriminating PAH patients with intermediate and high risk based on risk score | 12.32 | 19.36 |
0.008
|
Discriminating PAH patients with intermediate and high risk based on REVEAL 2.0 score | 7.33 | 10.07 | 0.098 |